IGCS 2012

OCTAVIA trial: bevacizumab and paclitaxel treatment for ovarian cancer

Dr Antonio Gonzalez-Martin – MD Anderson Cancer Center, Madrid, Spain

Antonio, you’re from the MD Anderson but not the one in Texas, you’re from the one in Madrid. You’ve been working on OCTAVIA which is a study that follows on from some pretty interesting stuff about bevacizumab or chemotherapy in ovarian cancer. Can you tell me what you were doing in this study?

OCTAVIA was a combination of two strategies for the treatment of ovarian cancer. We know that the addition of bevacizumab to a standard three-week Taxol and carbo has improved efficacy and also a change in the administration of paclitaxel in a dose dense regimen when you give paclitaxel weekly although better than ever three weeks, at least in one randomised trial. So what we did was to combine both the strategies. Behind that design it was also the hypothesis that paclitaxel weekly has some kind of anti-angiogenic effect that could be synergistic with the anti-angiogenic effect of bevacizumab. So we included patients with ovarian cancer, the same inclusion criteria as in the ICON 7 trial. All the patients received carboplatin cue three weeks AU6F6 (?); all the patients received paclitaxel, 80mg/m2 every week and all the patients received bevacizumab, exactly the same as in the ICON 7 trial.

So it was a single arm trial?

It was single arm trial, it was a single arm trial. The endpoint of this trial was progression free survival and we included 189 patients, 189 patients, which is a large phase II trial.

Now the ICON 7 study, of course, was double, was a blinded trial, was a controlled trial.

It was a randomised trial but not a blind trial.

Yes, but OCTAVIA is single arm; what is your reason for having a single arm study?

When we decided to perform this combination we asked for some support in order to perform a randomised trial but at that moment all the trials with bevacizumab were launched. So the idea was just to provide some data of efficacy and safety regarding the combination of these two strategies.

OK. You were hoping for an anti-angiogenic effect from the paclitaxel too, so what actually happened in your study?

Really it was very nice to observe several things. The first is that the regimen is feasible. Actually 90% of patients were able to complete the chemotherapy phase, the six cycles of chemotherapy, which is important because in the Japanese trial giving the same schedule they had to stop therapy in one third of the patients or one third of the patients didn’t complete the therapy. The second observation is that the toxicity in this trial is very consistent with the toxicity observed in other phase III trials with bevacizumab in front line, for instance ICON 7. And the third observation is that the median progression free survival that we have reached is 23.7 months. The lower limit of the 90% confidence interval was higher than 18 months and was higher than the median progression free survival in ICON.

Now can you put that in perspective? You said higher than in ICON, so you got a fairly good result although you haven’t strictly got controls?

Yes. We cannot compare both trials because it is not a randomised trial but just to put it in context, the same population, the same inclusion criteria, the same dose of bevacizumab and duration in the ICON 7 provides a median progression free survival of 19 months and in our trial was 23.7 months. Just to put into context the data.

What is this telling us, first of all, about the use of bevacizumab and also about things like the weekly paclitaxel?

I think that probably one of the most important questions that need to be answered in the near future is the best way to give paclitaxel to the patients. The ICON 8 trial, which is a trial allowed by the United Kingdom MRC group, is addressing this question, it’s addressing this question, but our perception is that probably weekly paclitaxel is the correct way to give paclitaxel to the patients with ovarian cancer and that the combination may be a step forward in the treatment of the patients.

How much does the bevacizumab add, do you think?

It’s a very difficult question to answer because we don’t have a single arm without bevacizumab in this group of patients. So what we can say is that when you add bevacizumab to the every three weeks schedule you improve your median progression free survival. If you change the paclitaxel you also improve the median progression free survival, that’s the only thing that we can say.

What do you think might be the impact on overall survival?

Really that’s again a difficult question to answer in a single arm study, in a single arm study. For example, in our study the rate of patients alive at two years is 92% which, for example, in comparison with the data of the Japanese trial, just to put into context, not to compare, it seems higher. So we don’t know.

So what is this telling the cancer doctor at this point in time?

What this is telling is that the future in ovarian cancer should come from the combination of different strategies. The era of paclitaxel and carboplatin every three weeks has gone and we have to move forward. Probably the combination of strategies is the correct way.

So what are the clinical implications that doctors should apply in their everyday practice from now? The story isn’t finished, is it?

Yes, I would say that just with a little change in the way to give paclitaxel you can improve the outcome of your patients. So it’s not a huge change, it’s not a huge change also in the cost, and probably we will see better outcome of the patients but we still need confirmatory trials in the Caucasian population.

You had a relatively small number of patients so you might have got to actually see some of these patients, what do they say about the therapy?

I’m very happy about this schedule because I include several patients in this clinical trial and we still have more than 70% of patients two years after without progression. So my feeling was good during the therapy and my feeling is good in the follow-up of the patients but that’s only my perception of the patients that I included in the trial.

But ovarian cancer isn’t easy so what’s your overall conclusion from this?

My overall conclusion is that we are now in the correct way after fifteen years of treatment of ovarian cancer with the same therapy.

And, of course, other anti-angiogenics, do you see those on the horizon?

There are other anti-angiogenics in the field now under investigation, for example AMG306 and tyrosine kinase inhibitors, but we don’t have data of the efficacy of those trials. For example, this morning has been presented a randomised trial with sorafenib showing no benefit so not all the anti-angiogenic therapies are similar.

Well a very interesting and very optimistic story. Antonio, thank you for joining ecancer.tv.